Concepts proposed regarding the physiologic control of the volume of blood held by the systemic veins in humans and how venous volume is modified by drugs have been derived from canine experiments and "venous tone" studies of human limbs (predominately veins draining skin and skeletal muscle). Since muscle veins are not innervated and cutaneous veins are primarily for thermoregulation, one must question the relevance of limb venous tone studies to the understanding of venous return in humans. The third large venous bed that undoubtedly plays a major role in regulating venous return, the splanchnic veins, has not been studied in humans. The importance of the splanchnic venous system, however, has been emphasized in canine studies. These have provided a reasonable model of the circulation as a single pump perfusing two parallel channels with different time constants (RvC) (the product of systemic venous resistance, Rv, and systemic venous compliance, C). The channel with the longer time constant best describes the splanchnic circulation. Since domestic dogs (as well as fur seals and raccoons) have "hepatic venous sphincters" which contribute significantly to splanchnic venous resistance, the relevance of canine studies to human venous control mechanisms must also be questioned. Therefore, the studies proposed in this grant are designed to determine if the mechanical parameters that regulate venous return (Rv,C) in humans and swine are qualitatively or quantitatively similar to dogs and if they change similarly with physiologic (systemic cooling, tilting) and pharmacologic (vasodilator, vasoconstrictor) interventions. Rv and C will be calculated during cardiopulmonary bypass from the rate of venous return to the reservoir of the oxygenator during step reductions of right atrial pressure (reservoir height) at a constant pump flow. Simultaneously, venous return from the leg will be measured by plethysmography and limb "venous tone" calculated by the equilibration and acute occlusion techniques. Thus, it is expected that two large bodies of information can be related (venous return studies in dogs and venous tone studies done on the limbs of humans) and provide, for the first time, a clear understanding of how venous return is regulated in humans.